NKG2D受体通过与青少年异常性关节炎患者的树突细胞相互作用来调节CD4+T细胞分化
Juan Zhou1, Junyan Wang2, Linlin Tao3
1Department of Pediatric Allergy, Immunology & Rheumatology, Guangzhou Women and Children's Medical Center, Guangdong, Provincial Clinical Research Center for Child Health, Guangzhou, China.
Clinical immunology (Orlando, Fla.)
|September 23, 2023
概括
自然杀手组2D (NKG2D) 受体在青少年异常性关节炎 (JIA) 中发挥着关键作用. 它影响T细胞激活和树突细胞成熟,影响疾病活动和亚型.
科学领域:
- 免疫学 免疫学 免疫学
- 类风湿病学 类风湿病学
- 细胞生物学 细胞生物学
背景情况:
- 自然杀手组2D (NKG2D) 是一种提供T细胞激活共刺激信号的受体.
- 它在青少年异常性关节炎 (JIA) 中CD4+T细胞和树突细胞 (DCs) 之间的相互作用中的确切作用仍然不完全理解.
研究的目的:
- 在JIA的背景下,研究NKG2D在CD4+T细胞和DC相互作用中的功能.
- 阐明NKG2D信号如何影响JIA患者的T细胞分化和DC成熟.
主要方法:
- 使用NKG2D转基因CD4+T细胞进行实验分析.
- 在JIA患者 (关节和全身亚型) 和健康对照者之间,对T细胞的NKG2D表达和DC上的MICA/MICB表达进行了比较.
- 在CD4+T细胞中评估了细胞因子 (IL-12,IL-10,TGF-β,IFN-γ,IL-17,IL-4) 和转录因子表达 (RORc,T-bet,Foxp3,GATA3).
- 评估的直流成熟标记 (CD83) 和配体表达 (MICA,MICB).
主要成果:
- 与健康对照组相比,活跃的JIA患者表现出CD4+NKG2D+T细胞的频率显著更高.
- 在关节性JIA和系统性JIA中观察到CD4+ T细胞的NKG2D表达升高和DCs上的MICA/MICB表达.
- 在CD4+T细胞中NKG2D信号促进了IL-12的产生,抑制了IL-10和TGF-β,并通过上调RORc和T-bet来偏向IFN-γ+和IL-17+T细胞的分化,同时降低了调控性T细胞标记物 (CD25,Foxp3) 和IL-4的产生.
- 在DC上NKG2D信号导致IL-10降低,并增加CD83,MICA和MICB表达在JIA患者和对照组中.
结论:
- 在JIA中,NKG2D直接调节CD4+T细胞分化.
- NKG2D间接影响树突细胞成熟,这表明它在调节JIA病原体内的免疫反应方面发挥了双重作用.
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